Aix Marseille University, CNRS, INSERM, CIML, Marseille, France.
J Cell Sci. 2022 Dec 1;135(1). doi: 10.1242/jcs.259183. Epub 2022 Jan 10.
When intracellular, pathogenic Salmonella reside in a membrane compartment composed of interconnected vacuoles and tubules, the formation of which depends on the translocation of bacterial effectors into the host cell. Cytoskeletons and their molecular motors are prime targets for these effectors. In this study, we show that the microtubule molecular motor KIF1Bβ (a splice variant of KIF1B), a member of the kinesin-3 family, is a key element for the establishment of the Salmonella replication niche as its absence is detrimental to the stability of bacterial vacuoles and the formation of associated tubules. Kinesin-3 interacts with the Salmonella effector SifA but also with SKIP (also known as PLEKHM2), a host protein complexed to SifA. The interaction with SifA is essential for the recruitment of kinesin-3 on Salmonella vacuoles whereas that with SKIP is incidental. In the non-infectious context, however, the interaction with SKIP is essential for the recruitment and activity of kinesin-3 only on a fraction of the lysosomes. Finally, our results show that, in infected cells, the presence of SifA establishes a kinesin-1 and kinesin-3 recruitment pathway that is analogous to and functions independently of that mediated by the Arl8a and Arl8b GTPases. This article has an associated First Person interview with the first author of the paper.
当细胞内的致病性沙门氏菌驻留在由相互连接的空泡和小管组成的膜隔室中时，这些空泡和小管的形成取决于细菌效应蛋白向宿主细胞的易位。细胞骨架及其分子马达是这些效应蛋白的主要靶点。在这项研究中，我们表明微管分子马达 KIF1Bβ（KIF1B 的剪接变体），一种驱动蛋白-3 家族的成员，是建立沙门氏菌复制生态位的关键要素，因为其缺失不利于细菌空泡的稳定性和相关小管的形成。驱动蛋白-3 与沙门氏菌效应蛋白 SifA 相互作用，但也与 SKIP（也称为 PLEKHM2）相互作用，SKIP 是与 SifA 结合的宿主蛋白复合物。与 SifA 的相互作用对于将驱动蛋白-3 募集到沙门氏菌空泡上是必不可少的，而与 SKIP 的相互作用则是偶然的。然而，在非感染性环境中，与 SKIP 的相互作用对于驱动蛋白-3 仅在部分溶酶体上的募集和活性是必不可少的。最后，我们的结果表明，在感染细胞中，SifA 的存在建立了一种驱动蛋白-1 和驱动蛋白-3 的募集途径，该途径与由 Arl8a 和 Arl8b GTPases 介导的途径类似且独立运作。本文附有对该论文第一作者的第一人称采访。
